The goal of this program is to develop derG as a therapeutic and/or prophylactic agent for HSV infections. DerG is a small peptide shown in preliminary experiments to elicit anti-viral and anti-parasitic (malarial) responses, and adjuvant activity. Based upon its structure, derG should bind to CD4 molecules. Its broad spectrum of activity suggests that it has a novel action on the innate or adaptive immune system's early events before antigenic challenge. This agent, derG, would be useful for treatment of medically important viral and other infections for which there may not be treatment or vaccine, or the treatment is too toxic or of limited efficacy. This peptide, or similar peptides, with immunoenhancing or adjuvant activity will be evaluated as potential clinical candidates to be used as a drug to provide broad spectrum protection against otherwise untreatable infectious agents. This may be useful prior to travel or assignment to a region of high risk for exposure or immediately after initial contact such as with sexually transmitted diseases or other infectious agents. Efforts in this study will focus on the herpes simplex viruses with the recognition that the resultant outcome may be an agent that will also have application for other infectious diseases as either a prophylactic or a therapeutic agent. The specific aims of the phase I are as follows: Specific Aim 1. In Vivo Activity: Evaluate the protection afforded by derG in animal models of HSV 1 disease as a function of the route (subcutaneous, intraperitoneal, intramuscular), dose amount and vehicle (saline or emulsion) and timing of derG administration to optimize treatment for the accomplishment of future specific aims. Specific Aim 2. Determine the cell types responsible for initiating and mediating derG induced protection (innate, inductive and effector) and the mechanism (cytokine release) by which protection occurs during HSV challenge by the scarification-zosteriform spread model of disease. Demonstrate the importance of CD4, CD8, CD86(B7-1), CD80 (B7-2), and CD40 expressing cells following treatment with various monoclonal antibody or surface receptor ablating-blocking reagents. If successful the phase II program will evaluate derG in a HSV genital infection model and test derG on HSV I and HSV II strains in both inbred and outbred animals. An integral part of the phase II program will be to further elucidate the target cells and mechanism of action of derG.